Search Results (184)

Background/Objectives: Diamine oxidase (DAO) enzyme metabolizes dietary histamine in the gastrointestinal tract. DAO deficiency can lead to histamine intolerance (HIT), manifesting as migraines, gastrointestinal disturbances, and allergic reactions. DAO supplementation has been shown to enhance histamine breakdown, alleviating these symptoms. This randomized, double-blind, single ascending dose (SAD) Phase I clinical trial aimed to evaluate the safety and tolerability of escalating doses of DAO supplementation in healthy volunteers. Methods: Thirty participants were randomly assigned to receive single doses of 42 mg, 84 mg, or 210 mg of DAO extract (adiDAO^® Veg) or placebo under fasting conditions. Vital signs, laboratory parameters, and adverse events (AEs) were monitored. Results: No serious adverse events or clinically significant changes in vital signs, ECGs, or laboratory parameters were observed. Conclusions: This trial confirms the safety and tolerability of high-dose DAO supplementation. Future studies are recommended to explore the effects of chronic high-dose administration and alternative dosage forms to improve convenience. Full article

The C=C double bond is a typical feature in biodiesel components associated with their physicochemical behaviors, including metal degradation. In this work, copper was exposed to the gas-phase atmospheres of Methyl Hexanoate (MH) at 145 °C and 25% Methyl Trans-3-Hexenoate in Methyl Hexanoate (MT3H in MH) at 158 °C during 1000 h, representing saturated and unsaturated thermal degradation environments of biodiesel surrogates. FTIR, ¹H NMR, and GC-MS were used to characterize the chemical changes in the gas-phase atmospheres, whereas SEM allowed us to inspect the copper surfaces. Weight loss assays enabled the estimation of corrosion rates for copper exposed to HM and MT3H in MH atmospheres of 3.81 ± 1.27 and 5.08 ± 1.27 μm/year, respectively. Electrochemical measurements (linear polarization resistance (LPR) and electrochemical impedance spectroscopy (EIS)) were used to evaluate the corrosion behavior of copper using aqueous extracts of condensed compounds from gas-phase degraded environments. Our electrochemical results indicate that similar corrosion processes occur in both extracts, remaining nearly unchanged with increasing exposure time. A porous layer of corrosion products on copper revealed that it is more active in the products generated with the MT3H in MH extract, suggesting the significant impact of the C=C bond on copper deterioration. Full article

Biogenic amines (BAs) are nitrogenous compounds naturally present in protein-rich foods, whose accumulation may indicate spoilage and pose health risks. This study presents the development and validation of a rapid LC–MS/MS method for the simultaneous quantification of six BAs—putrescine (PUT), cadaverine (CAD), histamine (HIS), tyramine (TYR), spermidine (SPD), and spermine (SPM)—in meat products, without requiring derivatisation. Sample preparation was optimized to enhance extraction efficiency and reproducibility, using 0.5 M HCl and a double-centrifugation protocol to avoid matrix interference. Chromatographic separation was optimized using a C18 column and acidified ammonium formate/acetonitrile mobile phases. The method showed good linearity (R² > 0.99), trueness between −20% and +20%, and acceptable precision (RSD_r and RSD_R ≤ 25%). Limits of quantification were established at 10 µg/g for all analytes. The method was applied to ten commercial meat samples, where PUT, TYR, and SPD were the most frequently detected amines. Although HIS and TYR levels were below toxicological thresholds for healthy individuals, one sample showed TYR levels potentially concerning for monoamine oxidase inhibitors -treated consumers. The Biogenic Amine Index (BAI) further supported product quality assessment, identifying early spoilage in selected cases. This method offers a rapid, robust and efficient tool for routine monitoring of BAs in meat products, supporting food safety and quality control initiatives. Full article

Olive mill wastewaters (OMWW) generated during olive oil extraction represent a significant environmental challenge due to their high organic matter content, acidic pH, phenolic content, and toxicity. Their composition varies widely depending on the extraction method and remains difficult to treat, particularly for small-scale producers lacking access to complex infrastructure. This study evaluates the combined effect of the extraction system (traditional vs. three-phase continuous) and filtration level (single vs. double) on the physicochemical and biological properties of OMWW. The methodologies employed included the analysis of water content, density, fatty acid composition, acidity, pH, total solids, chemical and biochemical oxygen demand, and biodegradability. The results indicate that traditional systems consistently produced OMWW with higher organic matter and phenolic loads, while filtration moderately reduced antioxidant potential and acidity, especially in traditional systems. The use of simple, low-cost filtration materials proved effective in improving effluent clarity and could serve as a practical pre-treatment option. This approach offers an accessible strategy for small producers aiming to valorise OMWW or reduce environmental impact. However, the study was conducted at the laboratory scale, and the long-term behaviour of filtered OMWW under real operating conditions remains to be evaluated. Full article

Mistletoe (Viscum album L.) has been used in complementary cancer therapy for decades, but its mechanisms remained poorly understood until recently. This review synthesizes transformative advances in mistletoe cancer research from 2020 to 2025, focusing on newly discovered molecular mechanisms, immunomodulatory properties, and clinical applications. We conducted a comprehensive analysis of controlled studies, mechanistic investigations, and real-world evidence published between 2020 and 2025. The discovery of mistletoe-induced immunogenic cell death (ICD) represents a paradigm shift in understanding its anticancer effects. Mistletoe extracts trigger endoplasmic reticulum stress, leading to calreticulin exposure in 18–51% of cancer cells and a 7-fold increase in adenosine triphosphate (ATP) release. Three-dimensional culture models revealed enhanced macrophage reprogramming effects, with a 15.8% increase in pro-inflammatory interleukin (IL)-6 and a 26.4% reduction in immunosuppressive IL-10. Real-world evidence from over 400 non-small-cell lung cancer patients shows that combining mistletoe with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors doubles median overall survival (6.8 to 13.8 months), with biomarker-selected populations experiencing up to a 91.2% reduction in death risk. The Johns Hopkins Phase I trial established intravenous administration safety at 600 mg three times weekly. Advanced analytical approaches including metabolomics, chronobiology, and machine learning are enabling precision medicine applications. These findings position mistletoe as a scientifically validated component of integrative oncology, bridging traditional medicine with evidence-based cancer care. Future research should focus on ferroptosis mechanisms, single-cell immune profiling, and standardized clinical protocols. Full article

Plasmid DNA (pDNA) purification plays a key role in the development of vaccines and gene therapies. Affinity chromatography stands out as a promising method for plasmid purification, leveraging a range of biological and synthetic ligands to achieve selectivity. This study investigates the potential of a synthetic ligand library consisting of triazine-based bifunctional compounds designed to mimic the side chains of amino acids that are known to bind nucleic acids. A high-throughput screening method was employed to assess the binding ability of 158 ligands within the library to single-stranded, FITC-labeled homo-oligonucleotides (G and T), each comprising 20 nucleotides, under both hydrophilic and hydrophobic conditions. High-affinity ligands were identified for both T and G oligonucleotides. Follow-up microscale chromatographic screening uncovered some false positives from the initial FITC-based screening, narrowing the selection to 22 ligands for further investigation. In the next phase of the study, the binding affinity of these ligands towards double-stranded oligonucleotides (AT and CG) was assessed. Ligand 1/2, a mimic of Ala-Lys or Gly-Lys, and ligand 2/3, a mimic of Lys-Tyr, were chosen as initial candidates for evaluating plasmid DNA purification from an Escherichia coli crude extract. The results obtained with 0.4 M ammonium sulfate in 20 mM Tris-HCl (pH 8.0) as the binding buffer were similar to those observed when purifying plasmid DNA from E. coli clarified lysates by hydrophobic interaction chromatography. The affinity resins retained RNA, while the less hydrophobic plasmid DNA was excluded in the initial fractions. Future research will be directed towards exploring the potential of the most promising ligands to separate pDNA isoforms. Full article

A novel type of multifunctional hybrid membranes combining modified chitosan, functionalized multi-walled carbon nanotubes (MWCNTs), and rare earth element ion-imprinted polymers (REEIIPs) were designed and characterized. The synthesized materials were characterized by thermogravimetric analysis (TGA), scanning electron microscopy (SEM), vibrating sample magnetometry (VSM), X-ray diffraction (XRD), X-ray micro-tomography, and Fourier transform infrared spectroscopy (FTIR). The hybrid membranes were also studied in terms of their mechanical and rheological properties. The key element of the proper preparation of hybrid membranes using the casting method in an external magnetic field was to synthesize membrane components with appropriate magnetic properties. It was found that they showed tunable weak ferromagnetic properties, and the increase in modified nanotube addition caused the rise in the membrane’s saturation magnetization, which for Nd-selective hybrid membranes reached 0.44 emu/g. Also, the increase in thermooxidative stability was noted after introducing functionalized nanotubes into polymer matrices, which, in the case of Gd-selective membranes, were stable even up to 730 °C. The rise in the modified MWCNT addition and selection of appropriate REE ion-imprinted polymers improved mechanical (Rm and E values increase even twice) and rheological parameters (almost double growth of E′ and E″ values) of the tested membranes. Synthesized hybrid membranes showed a high rejection of matrix components and an increase in retention ratio with rising MWCNT-REEIIP addition, ultimately reaching 94.35%, 92.12%, and 90.11% for Nd, Pr, and Gd, respectively. The performed analysis confirmed homogeneous dispersion, phase compatibility, network integration, formation of a complex 3D microstructure, and improved operational stability of created hybrid membranes, which is significant for their future applications in Nd, Pr, and Gd recovery from coal fly ash extracts. Full article

Background: Pre-season training is critical for developing tolerance to high physical demands in professional soccer, and nitric oxide (NO) precursors such as dietary nitrate (NO₃⁻) and citrulline malate (CM) can support performance and recovery during this demanding phase. This study aimed to examine the effects of a four-week supplementation protocol combining 500 mg of NO₃⁻ from amaranth extract and 8 g of CM (NIT + CM) on external training load and post-match recovery in professional female soccer players during pre-season. Methods: A randomized, double-blind, placebo-controlled trial was conducted with 34 female soccer players who received either the NIT + CM product or a placebo for four weeks during pre-season. Global positioning system (GPS)-derived external load was recorded throughout the intervention. Performance tests—a countermovement jump (CMJ) test and the Wingate anaerobic test (WAnT)—and blood sampling for plasma NO₃⁻ and nitrite (NO₂⁻) concentrations were conducted at baseline and the day after a competitive match. Results: The supplementation with NIT + CM increased maximal speed (Vmax) throughout training and match play. During post-match testing, the NIT + CM group exhibited a significantly smaller decline in mean (P_mean) and minimum (P_min) power during the WAnT, along with reduced power loss in both the first (0–15 s) and second (15–30 s) intervals. Plasma NO₃⁻ concentrations significantly increased from baseline in the NIT + CM group and remained elevated 24 h after the final dose, confirming sustained systemic exposure. Conclusions: Chronic NIT + CM supplementation may enhance Vmax and help preserve anaerobic performance the day after a match. These effects could reflect improved tolerance to high training loads and sustained NO₃⁻ availability during recovery. Full article

This study proposes a hybrid approach combining threshold-based algorithm and deep learning to detect four major gait events—initial contact (IC), toe-off (TO), opposite initial contact (OIC), and opposite toe-off (OTO)—using only a smartphone’s built-in inertial sensor placed in the user’s pocket. The algorithm enables estimation of spatiotemporal gait parameters such as cadence, stride length, loading response (LR), pre-swing (PSw), single limb support (SLS), double limb support (DLS), and swing phase and symmetry. Gait data were collected from 20 healthy individuals and 13 hemiparetic stroke patients. To reduce sensitivity to sensor orientation and suppress noise, sum vector magnitude (SVM) features were extracted and filtered using a second-order Butterworth low-pass filter at 3 Hz. A deep learning model was further compressed using knowledge distillation, reducing model size by 96% while preserving accuracy. The proposed method achieved error rates in event detection below 2% of the gait cycle for healthy gait and a maximum of 4.4% for patient gait in event detection, with corresponding parameter estimation errors also within 4%. These results demonstrated the feasibility of accurate and real-time gait monitoring using a smartphone. In addition, statistical analysis of gait parameters such as symmetry and DLS revealed significant differences between the normal and patient groups. While this study is not intended to provide or guide rehabilitation treatment, it offers a practical means to regularly monitor patients’ gait status and observe gait recovery trends over time. Full article

Rare earth elements (REEs) have garnered significant global attention due to their essential role in advanced technologies. Sri Lanka is endowed with various REE-bearing minerals, including the apatite-rich deposit in the Eppawala area, commonly known as Eppawala rock phosphate (ERP). However, direct extraction of REEs from ERP is technically challenging and economically unfeasible. This study introduces a novel, integrated approach for recovering REEs from ERP as a by-product of nitrophosphate fertilizer production. The process involves nitric acid-based acidolysis of apatite, optimized at 10 M nitric acid for 2 h at 70 °C with a pulp density of 2.4 mL/g. During cooling crystallization, 42 wt% of calcium was removed as Ca(NO₃)₂.4H₂O while REEs remained in the solution. REEs were then selectively precipitated as REE phosphates via pH-controlled addition of ammonium hydroxide, minimizing the co-precipitation with calcium. Further separation was achieved through selective dissolution in a sulfuric–phosphoric acid mixture, followed by precipitation as sodium rare earth double sulfates. The process achieved over 90% total REE recovery with extraction efficiencies in the order of Pr > Nd > Ce > Gd > Sm > Y > Dy. Samples were characterized for their phase composition, elemental content, and morphology. The fertilizer results confirmed the successful production of a nutrient-rich nitrophosphate (NP) with 18.2% nitrogen and 13.9% phosphorus (as P₂O₅) with a low moisture content (0.6%) and minimal free acid (0.1%), indicating strong agronomic value and storage stability. This study represents one of the pioneering efforts to valorize Sri Lanka’s apatite through a novel, dual-purpose, and circular approach, recovering REEs while simultaneously producing high-quality fertilizer. Full article

Horizontal wells have revolutionized hydrocarbon production by enhancing recovery efficiency and reducing environmental impact. This paper presents an enhanced Black Oil Model simulator, written in Visual Basic, for three-dimensional two-phase (oil and water) flow through porous media. Unlike most existing tools, this simulator is customized for horizontal well modeling and calibrated using extensive historical data from the South Rumaila Oilfield, Iraq. The simulator first achieves a strong match with historical pressure data (1954–2004) using vertical wells, with an average deviation of less than 5% from observed pressures, and is then applied to forecast the performance of hypothetical horizontal wells (2008–2011). The results validate the simulator’s reliability in estimating bottom-hole pressure (e.g., ±3% accuracy for HRU1 well) and water–oil ratios (e.g., WOR reduction of 15% when increasing horizontal well length from 1000 m to 2000 m). Notably, the simulator demonstrated that doubling the horizontal well length reduced WOR by 15% while increasing bottom-hole pressure by only 2%, highlighting the efficiency of longer wells in mitigating water encroachment. This work contributes to improved reservoir management by enabling efficient well placement strategies and optimizing extraction planning, thereby promoting both economic and resource-efficient hydrocarbon recovery. Full article

Heterozygous mutations in the GBA1 gene, encoding the enzyme glucocerebrosidase (GCase), are major risk factors for Parkinson’s Disease (PD). Ambroxol, a small chaperone originally used as a mucolytic agent, has been shown to cross the blood–brain barrier, enhance GCase activity, and reduce α-synuclein levels, making it a promising therapeutic candidate for disease-modifying effects in GBA1-associated PD (GBA1-PD). This study aimed to develop a method to quantify ambroxol levels in human plasma and cerebrospinal fluid (CSF) using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Ambroxol was determined by online solid-phase extraction (SPE), coupled with LC-MS/MS, by gradient elution on a monolithic column. Detection employed a 3200 QTRAP tandem mass spectrometer in the positive electrospray ionization mode. Calibration curves exhibited linearity across the analyzed ranges in both plasma and CSF. The recovery rate ranged from 106.7% to 113.5% in plasma and from 99.0% to 103.0% in CSF. No significant matrix effect was observed. Intra-day and inter-day precisions were below 11.8% in both matrices, and accuracy ranged from 89.9% to 103.1% in plasma and from 96.3% to 107.8% in CSF. We evaluated and confirmed the stability of the analyte in plasma and CSF across various storage conditions. The method was successfully validated according to European Medicine Agency (EMA) guidelines and its applicability was confirmed in the context of a multicenter, randomized, double-blind, placebo-controlled, phase II study, designed to monitor the ambroxol levels in the plasma and CSF of GBA1-PD. Full article

In this study, we analysed cocoa (a dried and fully fermented seed of Theobroma cacao L.) from two Amazonian cultivars and a commercial sample of the Amazonian variety EETP801, grown under sustainable organic conditions, in comparison to CCN51 cocoa grown on a neighbouring commercial farm using standard practises and a European commercial cacao powdered beverage. The overall metabolite profile of the 70% aq acetone sample cocoa extracts was analysed using high-performance TLC analyses (HPTLC), and the xanthine alkaloids were analysed using quantitative liquid chromatography–UV photodiode array (HPLC-DAD) analyses. The volatile fraction in the headspace of the freshly ground cocoa was subjected to solid phase micro-extraction and analysed by gas chromatography–mass spectrometry (HS-SPME/GC-MS). Total polyphenol content was determined by the Folin–Ciocalteu method. Despite the reduced production of cocoa by the EETP801 cultivar in comparison with the CCN51 cultivar, the obtained produce is significantly richer in theobromine (130 mg vs. 170 mg per g of cacao), with CCN51 having a double concentration of theophylline (12.6 vs. 6.5 mg per g of cacao). Qualitatively, the two Amazonian cocoa samples had a similar polyphenolic composition (per the HPTLC fingerprint). HS-SPME/GC-MS analyses revealed that all the samples show a spontaneous emission profile mainly rich in non-terpene derivatives, of which hydrocarbons and pyrazines are the most abundant groups. The most represented volatile organic compound is n-tridecane for both EETP801 and CCN51. The variability in the artisan fermentation and roasting processes influenced certain aspects of the volatile composition as reflected by the trimethyl pyrazine/tetramethyl pyrazine ratio, which was zero in EETP-801 and lower than 1 in CCN51. Acetic acid was absent in CCN51 but significant (c.a. 5.5.%) in EETP801 and the commercial samples. The cultivar EETP801 is a viable option for a more ecologically conscious sector of the cocoa beverages consumer group. Full article

The central objective of this study is to develop some different wave solutions and perform a qualitative analysis on the nonlinear dynamics of the time-fractional chiral nonlinear Schrodinger’s equation (NLSE) in the conformable sense. Combined with the semi-inverse method (SIM) and traveling wave transformation, we establish the variational principle (VP). Based on this, the corresponding Hamiltonian is constructed. Adopting the Galilean transformation, the planar dynamical system is derived. Then, the phase portraits are plotted and the bifurcation analysis is presented to expound the existence conditions of the various wave solutions with the different shapes. Furthermore, the chaotic phenomenon is probed and sensitivity analysis is given in detail. Finally, two powerful tools, namely the variational method (VM) which stems from the VP and Ritz method, as well as the Hamiltonian-based method (HBM) that is based on the energy conservation theory, are adopted to find the abundant wave solutions, which are the bell-shape soliton (bright soliton), W-shape soliton (double-bright solitons or double bell-shaped soliton) and periodic wave solutions. The shapes of the attained new diverse wave solutions are simulated graphically, and the impact of the fractional order $\delta$ on the behaviors of the extracted wave solutions are also elaborated. To the authors’ knowledge, the findings of this research have not been reported elsewhere and can enable us to gain a profound understanding of the dynamics characteristics of the investigative equation. Full article

Diospyros kaki L. is acknowledged for its extraordinary phytotherapeutic properties due to the presence of polyphenols, carotenoids, and flavonoids such as β-cryptoxanthin and rutin. These compounds are largely distributed in the skin and flesh of the fruit. In this study, the different parts of persimmons were analyzed (whole fruit, peels, and flesh), aiming at determining total carotenoid and flavonoid content through selective extraction and HPLC-DAD analysis. Obtained by a one-pot double phase extraction, organic and aqueous extracts were submitted to colorimetric analyses and tested for their antifungal activity. Results indicated that carotenoid and flavonoid content varied with sample maturity, and colorimetry proved to be an effective predictor of pigments’ composition. The strongest antifungal and antibiofilm activity has been demonstrated for the hydroalcoholic extracts of the unripe whole fruit and flesh. Preliminary results suggest their potential application in preventing Candida infections by inhibiting their establishment. Although further studies are needed, these results open the way to the possible use of the extracts as additives in foods or in the preparation of pharmaceutical formulations for the prevention of infections caused by Candida albicans, helping to reduce the use of synthetic biocidal products. Full article